Low-energy electromagnetic processes affecting free-falling test-mass charging for LISA and future space interferometers

Galactic cosmic rays and solar energetic particles charge gold-platinum, free-falling test masses (TMs) on board interferometers for the detection of gravitational waves in space. The charging process induces spurious forces on the test masses that affect the sensitivity of these instruments mainly below $10^{-3}$ Hz. Geant4 and FLUKA Monte Carlo simulations were carried out to study the TM charging process on board the LISA Pathfinder mission that remained into orbit around the Sun-Earth Lagrange point L1 between 2016 and 2017. While a good agreement was observed between simulations and measurements of the TMs net charging, the shot noise associated with charging fluctuations of both positive and negative particles resulted 3-4 times higher that predicted. The origin of this mismatch was attributed to the propagation of electrons and photons only above 100 eV in the simulations. In this paper, low-energy electromagnetic processes to be included in the future Monte Carlo simulations for LISA and LISA-like space interferometers TM charging are considered. {It is found that electrons and photons below 100 eV give a contribution to the effective charging comparable to that of the whole sample of particles above this energy. In particular, for incident protons ionization contributes twice with respect to low energy kinetic emission and electron backscattering. The other processes are found to play a negligible role. For heavy nuclei only sputtering must be considered.Comment: Accepted for publication in Classical and Quantum Gravit

Bridging the gap between Monte Carlo simulations and measurements of the LISA Pathfinder test-mass charging for LISA

Cubic gold-platinum free-falling test masses (TMs) constitute the mirrors of future LISA and LISA-like interferometers for low-frequency gravitational wave detection in space. High-energy particles of Galactic and solar origin charge the TMs and thus induce spurious electrostatic and magnetic forces that limit the sensitivity of these interferometers. Prelaunch Monte Carlo simulations of the TM charging were carried out for the LISA Pathfinder (LPF) mission, that was planned to test the LISA instrumentation. Measurements and simulations were compared during the mission operations. The measured net TM charging agreed with simulation estimates, while the charging noise was three to four times higher. We aim to bridge the gap between LPF TM charging noise simulations and observations. New Monte Carlo simulations of the LPF TM charging due to both Galactic and solar particles were carried out with the FLUKA/LEI toolkit. This allowed propagating low-energy electrons down to a few electronvolt. These improved FLUKA/LEI simulations agree with observations gathered during the mission operations within statistical and Monte Carlo errors. The charging noise induced by Galactic cosmic rays is about one thousand charges per second. This value increases to tens of thousands charges per second during solar energetic particle events. Similar results are expected for the LISA TM charging.Comment: 11 pages, 9 figure

Clinical utility of continuing trastuzumab beyond brain progression in HER-2 positive metastatic breast cancer

No abstract availabl

Study of Galactic Cosmic-Ray Flux Modulation by Interplanetary Plasma Structures for the Evaluation of Space Instrument Performance and Space Weather Science Investigations

The role of high-energy particles in limiting the performance of on-board instruments was studied for the European Space Agency (ESA) Laser Interferometer Space Antenna (LISA) Pathfinder (LPF) and ESA/National Astronautics and Space Administration Solar Orbiter missions. Particle detectors (PD) placed on board the LPF spacecraft allowed for testing the reliability of pre-launch predictions of galactic cosmic-ray (GCR) energy spectra and for studying the modulation of proton and helium overall flux above 70 MeV n − 1 on a day-by-day basis. GCR flux variations up to approximately 15% in less than a month were observed with LPF orbiting around the Lagrange point L1 between 2016 and 2017. These variations appeared barely detected or undetected in neutron monitors. In this work the LPF data and contemporaneous observations carried out with the magnetic spectrometer AMS-02 experiment are considered to show the effects of GCR flux short-term variations with respect to monthly averaged measurements. Moreover, it is shown that subsequent large-scale interplanetary structures cause a continuous modulation of GCR fluxes. As a result, small Forbush decreases cannot be considered good proxies for the transit of interplanetary coronal mass ejections and for geomagnetic storm forecasting

The role of low-energy electrons in the charging process of LISA test masses

The estimate of the total electron yield is fundamental for our understanding of the test-mass charging associated with cosmic rays in the Laser Interferometer Space Antenna (LISA) Pathfinder mission and in the forthcoming gravitational wave observatory LISA. To unveil the role of low energy electrons in this process owing to galactic and solar energetic particle events, in this work we study the interaction of keV and sub-keV electrons with a gold slab using a mixed Monte Carlo (MC) and ab-initio framework. We determine the energy spectrum of the electrons emerging from such a gold slab hit by a primary electron beam by considering the relevant energy loss mechanisms as well as the elastic scattering events. We also show that our results are consistent with experimental data and MC simulations carried out with the GEANT4-DNA toolkit

Liver toxicity after treatment with gefitinib and anastrozole: drug-drug interactions through cytochrome p450?

No abstract availabl

HER2/neu expression and hormonal therapy in early breast cancer: can muddy waters become clear?

We have read with great interest the paper by Love et al [1] about the relationship between HER2/neu expression and response to adjuvant endocrine therapy in premenopausal women with breast cancer. Whereas HER2/neu and estrogen receptor (ER) are believed to be important cell survival and cell death factors in human breast cancer, if and how they interact to confer resistance to hormone therapy is still in debate. Several observations are consistent with a major role for c-erbB2 in the development of endocrine resistance, considering also the HER2/neu acquired expression durin

Impact of celecoxib on capecitabine tolerability and activity in pretreated metastatic breast cancer: results of a phase II study with biomarker evaluation

Background: Preclinical evidence suggests that the cyclo-oxygenase-2 (COX-2) enzyme plays an important role in breast cancer progression. The aim of the present phase II study was to determine the activity and safety of the combination of the COX-2 inhibitor celecoxib with capecitabine in metastatic breast cancer (MBC) patients pretreated with anthracyclines and/or taxanes. Methods: Eligible patients received capecitabine 1,000 mg/m(2) twice daily on days 1-14 every 21 days and celecoxib 200 mg twice daily, continuously, until disease progression or unacceptable toxicity. Results: About 42 pretreated MBC patients were enrolled into the study. Median number of previous chemotherapy lines for metastatic disease was 2 (0-3). Seven patients (19%) responded to treatment while disease stabilization occurred in 17 patients (40.5%). Overall, 20 patients (47.5%) achieved clinical benefit [objective responses (CR) plus stable disease (SD) >/=6 months]. Median time to progression (TTP) and median overall survival (OS) were 5.2 and 17.8 months, respectively. Treatment was very well tolerated: grade 3 toxicities were observed in only five patients, respectively, and no grade 4 adverse events were reported. Celecoxib was never discontinued for toxicity. Analysis of COX-2 expression in the 22 patients with available tissue revealed a significantly longer TTP and OS for patients whose tumors over-expressed COX-2. Conclusions: The combination of capecitabine and celecoxib is active and safe in far advanced MBC patients. Interestingly, this association resulted in a lower-than-expected toxicity, as compared to single-agent capecitabine. The clinical relevance of COX-2 as determinant of sensitivity to treatment with celecoxib should be further evaluated in larger series of patients

Magnitude of risks and benefits of the addition of bevacizumab to chemotherapy for advanced breast cancer patients: Meta-regression analysis of randomized trials

<p>Abstract</p> <p>Background</p> <p>Although the addition of bevacizumab significantly improves the efficacy of chemotherapy for advanced breast cancer, regulatory concerns still exist with regard to the magnitude of the benefits and the overall safety profile.</p> <p>Methods</p> <p>A literature-based meta-analysis to quantify the magnitude of benefit and safety of adding bevacizumab to chemotherapy for advanced breast cancer patients was conducted. Meta-regression and sensitivity analyses were also performed to identify additional predictors of outcome and to assess the influence of trial design.</p> <p>Results</p> <p>Five trials (3,841 patients) were gathered. A significant interaction according to treatment line was found for progression-free survival (PFS, p = 0.027); PFS was significantly improved for 1^stline (Hazard Ratio, HR 0.68, p < 0.0001), with a 1-yr absolute difference (AD) of 8.4% (number needed to treat, NNT 12). A non-significant trend was found in overall survival (OS), and in PFS for 2^ndline. Responses were improved with the addition of bevacizumab, without interaction between 1^stline (Relative Risk, RR 1.46, p < 0.0001) and 2^ndline (RR 1.58, p = 0.05). The most important toxicity was hypertension, accounting for a significant AD of 4.5% against bevacizumab (number needed to harm, NNH 22). Other significant, although less clinically meaningful, adverse events were proteinuria, neurotoxicity, febrile neutropenia, and bleeding. At the meta-regression analysis for 1^st-line, more than 3 metastatic sites (p = 0.032), no adjuvant chemotherapy (p = 0.00013), negative hormonal receptor status (p = 0.009), and prior anthracyclines-exposure (p = 0.019), did significantly affect PFS.</p> <p>Conclusions</p> <p>Although with heterogeneity, the addition of bevacizumab to 1^st-line chemotherapy significantly improves PFS, and overall activity. Hypertension should be weighted with the overall benefit on the individual basis.</p